Infection of children with the human immunodeficiency virus type 1 (HIV-1) as a result of perinatal transmission is an important problem in the US and throughout the world. Transplacental transmission of HIV-1 appears to be a major route, but there is still a paucity of information about mechanisms of infection in the placenta and possible targets for preventive modalities. For this purpose, we have established a multidisciplinary group with expertise in the placenta, virology, immunology, cell biology, pathology, and perfusion methodology to apply several experimental in vitro systems to studies on HIV infection of the placenta. These systems include: organ cultures of chorionic villi, isolated syncytiotrophoblast microvilli, purified placental trophoblast and stomal macrophages (Hofbauer cells), and dual perfusion of isolated placental lobules. Conjoint use of these methods should permit a better ascertainment of the types of mature and premature placental cells which enable uptake, persistence, or replication of HIV-1 and its transport across the placenta. Together, these experimental systems should allow, under controlled and biosafety conditions, to study possible differences related to the amount, type, or form of virus, including variations in strains of viruses, whether lymphocytotropic or monocytotropic, and whether isolated from mothers whose babies became infected or not. In addition, other viral variables to be ascertained include virus in an extracellular or cell-associated (lymphocyte or monocyte) form, bound or not to IgG antibody. Thereafter, it will be possible to evaluate which one, or combinations, of these methods, would be most useful to determine the possible efficacy of intervention modalities at different target levels. Such models should also permit placental mechanisms of HIV-2 infection to be studied. In addition, particularly following efforts to prolong placental perfusion for several days under physiological conditions, it should also be possible to determine the influence of other transplacentally-transmitted microbial agents, e.g. cytomegalovirus. The models developed should be particularly useful to ascertain whether antibodies elicited by experimental vaccines would be likely to prevent transplacental transmission of virus from mother to fetus.